title: Identification of a novel missense (C7W) mutation of SOD1 in a large familial amyotrophic lateral sclerosis pedigree.
abstract: Mutations of Cu-Zn superoxide dismutase (SOD1) have rarely been identified in Chinese patients with amyotrophic lateral sclerosis (ALS). We recently initiated a program to screen mutations of SOD1, TARDBP, and C9orf72 genes, the most commonly mutated genes in ALS patients in Western countries, in Chinese ALS patients. In this study, we report a novel missense SOD1 mutation with a substitution of tryptophan for cysteine at the seventh amino acid (p.C7W, traditionally named p.C6W) based on HUGO Gene Nomenclature in a familial ALS pedigree. We also found that the activities of SOD1 were significantly decreased in the C7W patient and the carriers of the family, compared with the SOD1 activities of normal family members. Compared with reported C7G and C7S patients, analysis of phenotype revealed relatively mild disease phenotypes in C7W patients, which is correlated with less deteriorated alteration in protein structure. Like those of many other familial ALS families, variable clinical phenotypes in the C7W intrafamily suggest that potential genetic modifiers may contribute to this disease.
authors.affiliation: Department of Neurology, Chinese PLA General Hospital, Beijing 100857, China; Beijing Institutes of Life Science Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Wang
authors.forename: Wanshi
authors.initials: W
authors.lastname: Cai
authors.forename: Fang
authors.initials: F
authors.lastname: Cui
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Chen
authors.forename: Fengbiao
authors.initials: F
authors.lastname: Mao
authors.forename: Huajing
authors.initials: H
authors.lastname: Teng
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Jiesi
authors.initials: J
authors.lastname: Wang
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Sun
authors.forename: Xusheng
authors.initials: X
authors.lastname: Huang
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D002681:China; D003545:Cysteine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D014364:Tryptophan
chemical_list: C000606290:SOD1 protein, human; D014364:Tryptophan; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003545:Cysteine
keywords: Familial amyotrophic lateral sclerosis (FALS); Motor neuron disease; Novel SOD1 missense mutation